ANTEPARTUM DEPRESSION 10 - 13% : Major and Minor Depression (O’Hara, 1990; Gotlib et al, 1989;...
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Transcript of ANTEPARTUM DEPRESSION 10 - 13% : Major and Minor Depression (O’Hara, 1990; Gotlib et al, 1989;...
ANTEPARTUM DEPRESSION
• 10 - 13% : Major and Minor Depression• (O’Hara, 1990; Gotlib et al, 1989; Kumar 1984,
Evans et al 2001)
• Low SES and psychosocial stressors• (Hopfer et al 1995)
• Strongest Predictor of PPD• (Graff et al, 1991)
Psychiatric Disorders during Pregnancy and the Postpartum
Period
Margaret Spinelli, MD
Associate Prof Of Psychiatry
Director, Maternal Mental Health Program
ANTEPARTUM DEPRESSION
• Poor Appetite; Weight
• Insomnia
• Poor Prenatal Care
• Nicotine, Drugs and Alcohol
(Zuckerman et al, 1990)
ANTEPARTUM DEPRESSION
• Low birth weight• Prematurity• Growth retardation• Small for gestational age infants• Developmental delay
• (Flynn 2005; Bonari et al 2004; Kurki et al 2000; Zuckerman et al, 1990; )
PRENATAL DEPRESSION AND ANXIETY
ANXIETY>>>>> UTERINE ARTERY
RESISTANCE >>>>
• LOW BIRTH WEIGHT • INCREASED MISCARRIAGE• PREMATURITY• FETAL HYPOXIA
– (Glover and O’Connor 2002, Chung et al 2001, Wadhwa et al 1993 Teseira et al. 1999)
Antenatal Anxiety: effects on the fetus and child
• ALSPAC community sample – n=8,323 mother-infant
pairs
– Gestational Age: 32 weeks
– Behavioral problems at 4 and 7 years
(Glover V, 2003,BJM) )
cortisol
cortisol
DECISION ANALYSIS
RISK / BENEFIT ANALYSIS
• framed by clinician’s expertise and the patient’s values and treatment preferences
• **PLAN BEFORE PREGNANCY**• (Wisner et al 2000)
Antidepressant SSRIs: metanalysis
o Sertraline (Zoloft)
o Citalopram (Celexa)
o Fluoxetine (Prozac)
o no major malformationso +/- Neonatal toxicity
(Sivojelezova et al; 2005)
PAXIL
• Retrospective Epidemiological Study– 3,581 SSRI exposed pregnant women
• increased risk of major congenital malformations
– (OR 2.20; 95% CI: 1.34-3.63)
• increased risk for cardiovascular malformations– (OR 2.08; 95%CI: 1.03-4.23)
– Ventricular Septal Defect. (10/14)• (GSK: 2005)
TRICYCLICS (TCAs)
• Desipramine (DMI)
• Nortryptylline(NTP)
– Serum levels
– Neonatal toxicity +/-• Withdrawal sx.
• Anticholinergic effects
Neurodevelopment: TCA or SSRIs through fetal life
Mother- child pairs (15-71 mos.): Tricyclics: (n = 46) Fluoxetine: (n = 40) Control: (n = 36)
Results: TCA or SSRI:– NO difference in IQ (Baylor or Mc Carhty scales),– temperament, language, or behavior
Depression: duration>>>> low IQ episodes>>>> poor language development
– Nulman et al 2002
“Neonatal Withdrawal Syndrome” Databases of adverse drug events
• WHO Collaborating Center for Drug Monitoring– ID 74 Cases of “Neonatal Withdrawal Syndrome”– tremor, neonatal convulsions, abnormal crying
• (paroxetine (n=51), fluoxetine (10), sertraline (7), citalopram (6), venlafaxine (6)
• (Sanz et al; The Lancet, 2005)
• FDA Adverse Event Reporting System – 57 cases of neonatal withdrawal
– (paroxetine (n=35), fluoxetine (4), sertraline (8), citalopram (5), venlafaxine (3), fluvoxamine (2)
(CDER: 2004, meeting document)
SSRI Neonatal WD: Case Reports• 18 cases of SSRI
– 61% Paxil; 22% Prozac
• Exposure– (17-40 weeks gestation; median 40 wks)
• Onset of symptoms:– Tremor, increased muscle tone, irritability, resp distress
• birth to 3 weeks
• Duration of symptoms:• mean: 2 weeks
• SSRIs:– (paroxetine (n=11), fluoxetine (4), sertraline (1), citalopram (1),
venlafaxine (1)• (Moses-Kolko et al; JAMA, 2005)
Meta-analysis: 3rd TM exposure to SSRIs
• Neonatal Behavioral Syndrome;– Meta-analysis: 3rd TM: ( 9 cohort studies and 18 cases)
– Risk Ratio : 3.0 (95% CI, 2.0-4.4)– CNS, motor, respiratory and GI signs – Usually mild and time limited (2 weeks)– Managed with supportive care – Most involve fluoxetine and paroxetine– More severe: seizures, hyperpyrexia etc.
• (Moses-Kolko et al. JAMA, 2005)
Neonatal Adaptation after 3rd TM exposure to SSRIs
Neonatal Behavioral Syndrome;Special Care Nursery Admissions:
2.6 (95% CI, 1.4-4.7)
Overall respiratory difficulty:
2.3 (95% CI, 1.6-3.2)
– Incidence of Intubation: 0.3% (1/313)
– No neonatal deaths
• (Moses-Kolko et al. JAMA, 2005)
SSRIs and Persistent Pulmonary Hypertension of the Newborn
377 Infants born with PPHN
14 infants with late (>20 weeks) SSRI exposure were compared to
6 control infants with early (<20 weeks) or no exposure to SSRI.
Odds of PPHN with late exposure compared to early or no exposure :
6.1 (95% CI, 2.2-16.8)(Chambers et al, NEJM, 2006)
Absolute Risk of PPHN
• Limitations:– supports association; no cause effect relationship– small Ns– retrospective
RR = 6.1 (95% CI, 2.2-16.8)
Absolute Risk = 6-12/ 1000 births (0.6-1.2%)
Therefore 99% of women treated with an SSRI delivered infants without PPHN
How should these reports
impact clinical practice?
Recurrence Risk of MDD in women who discontinue antidepressant treatment
proximal to conception
Group Relapse
Discontinued 44/65 (68%)
Maintained 21/82 (25%)
Time to recurrence:
50% in 1st TM / 90% in 2nd TM(Cohen et al; JAMA, 2006)
ELECTROCONVULSIVE
THERAPY
• APA guidelines:
– Ob consult
– Gest age >10 weeks
– Maternal and fetal heart rate
– Ob present if high risk
– Faculties for fetal emergencies
– Monitor fetal movement
Herbals
NO CLINICAL DATA – St John’s Wort– SAMe– Valerian Root
+/-– Omega 3 Fatty Acids
Alternatives
• Acupuncture • (n=61)
• Active acupuncture, v. control acupuncture vs. massage
• Response rates 69% v.47% v.29%• (Manber et al 2004)
• VNS
Light Therapy for Pregnant Depressed Women
0
5
10
15
20
25
30
0 1 2 3 4 5
SIGH-SADHAM-D
Oren D, Wisner K, Spinelli M et al, 2002
Me
an
Dep
res
sio
n S
co
res
Weeks of Light Therapy
There are no clinical guidelines for effective treatment for
antepartum depression.
Interpersonal Psychotherapy forAntepartum Depression
(IPT-P)
(Spinelli and Endicott Am J Psychiatry 2003, 160:555-562)
NIMH Grant #1K20 MH01276-01
DEMOGRAPHICS(N=38)
AGE: 29.I0 ( + 6.20)GESTATION: 21.40 WKS. ( +7.20)INCOME:
• 50 % $5-25,OOO• 16% $25-40,000
RACE: LATINO : 66% ( 80% SPANISH SPEAKING) AFRICAN AMERICAN: 5% CAUCASIAN: 29%
IPT-P vs. PEP in Depressed Pregnant WomenEdinburgh Postnatal Depression Scale
(p=.005)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
10
12
14
16
18
20
22
IPT-P Phase
EP
DS
>>
>m
ore
dep
ress
ed
PEP IPT-P
IPT-P vs. PEP in Depressed Pregnant WomenMean HAM-D
(p=.021)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1610
12
14
16
18
20
22
24
26
IPT-P Phase
HA
M-D
PEPIPT-P
Clinical Global Impressions Recovery < 2
(P=.O11)
IPT-P PEP0
10
20
30
40
50
60
Fre
que
ncy
(%)
ANTEPARTUM INTERPERSONAL
PSYCHOTHERAPY AT 3 NEW YORK CITY SITES
NIMH Grant #RO1 MH 069915-01A2
DESIGN AND METHODS
NIMH 5 Year Clinical Treatment Trial
• Focus: Psychiatry into primary care– Treatment in OB department
• 3 NYC sites• 3 MFM faculty: co-PIs
– Dr. Jane Cleary-Goldman (Columbia)– Dr. Robin Kalish (Cornell)– Dr. Lois Brustman (St.Luke’s Roosevelt Hospital)
AIM
Assess the efficacy of a 12-week
bilingual treatment trial of
Interpersonal Psychotherapy for Antepartum Depression
vs. Parenting Education Program
for multi- ethnic/racial sample from 3 NYC sites
Antepartum Interpersonal Psychotherapy at 3 NYC Sites
• detect and treat antepartum depression
• prevent postpartum depression
• assess maternal fetal/ infant attachment
• evaluate feasibility of services as they relate to race, ethnicity and SES ($50/visit)
WHEN BONDING FAILS..
Depressed mother; Depressed child
• Poor Response to Infant Cues/ Lack of Warmth
• Insecure Attachment, Irritable
– (Biringen and Robinson, 1991; Zuckerman et al, 1990)
• Behavior Problems, Delayed Language
• Easily Angered– (Murray, 1991; Biringen and Robinson,
1991)
• Intellectual Deficits, Predisposition to Depression
– (Cogill et al, 1986;– Weissman et al, 1987)
Epidemiology of Postpartum Episodes
Postpartum Depression Prevalence: 10-20%
Across cultures (Kumar 1994)
Risk Factors: Personal and Family H/O depression
Prenatal depression**
Prominent symptoms: anxiety associated with distressing thoughts about infant safety Feelings of guilt and inadequacy about mothering Inability to sleep when infant sleeps lack of interest in baby, family or activities anxiety as bizarre thoughts and fears poor bonding, feel “detached” “numb” Thoughts of death or suicide
(DOH;OMH 2005; Flynn, 2005)
)
Treating Postpartum Depression
Fluoxetine (Prozac): Controlled trialSertraline (Zoloft); openVenlafaxine (Effexor): open Interpersonal PsychotherapyFluoxetine and CBT
Guidelines for Medicating during Lactation
• Avoid polypharmacy
• Monitor infant sleep, feeding
• Bottle feed if sick
• Lowest effective dose
• Collaboration with Pediatrician
• All pass to breast milk
– depends on drug and metabolite
– UK outcome on physiology, behavior and development
Benefits of BreastfeedingProvides immunity
Allergies, asthmaOtitis media
Viral diarrhea
RSV morbidity
Upper and lower respiratory infection
Childhood lymphoma, Type I DM, Crohn’s
IQ: 8-12 points
BREASTFEEDING AND ANTIDEPRESSANTS
• SSRIs: first line – Few adverse effects to date
– Infant serum: minimal or no drug or metabolite***
• TCAs: second line– NTP (least detected in infant serum)
– Limitations:• Small Ns, case reports, no long term effects
• ***does not apply to fluoxetine/ venlafaxine
BREASTFEEDING AND ANTIDEPRESSANTS
Celexa: Elevated infant levels
‘uneasy sleep”
Serum Fluoxetine accumulation long T ½: accumulation in infant serum
Immature infant enzymes
Irritability
BREASTFEEDING AND ANTIDEPRESSANTS
Sertraline
usually yields undetectable infant serum levels
No adverse effects
Maternal 5HT concentration decreased with sertraline but infant platelet 5HT transport not affected c/w undetectable levels in infant serum.
• (Epperson 2003)
BENZODIAZEPINES AND LACTATION
• Neonatal Risks (Burt et al. AJP 2001)
– withdrawal, sedation, cyanosis
• Guidelines– low dose, monotherapy– split dosing– discard feeding at peak drug level; – formula supplementation– short-acting, low metabolites
• Alternative:– Nortryptylline (NTP)
POSTPARTUM PSYCHOSIS
auditory hallucinations (baby; religious) visual hallucination (seeing or feeling a presence) agitation, irritability paranoid delusions delirium (waxing and waning) confusion mania suicidal or infanticidal thoughts bizarre delusions
POSTPARTUM PSYCHOSISHIPPOCRATES 4TH CENTURY “LACTATIONAL PSYCHOSIS”
PREVALENCE– 1-2/1000– 70% IN THE FIRST 2 WEEKS– BIPOLAR EPISODE ****– (<5% SCHIZOPHRENIA)
QUALITIES– ORGANIC SYMPTOMS – WAXING & WANING/ AMNESIA
RISK: INFANTICIDE RECURRENCE: 30-50%
“PROPHYLAXIS”: PP LITHIUM OR OTHER
““Cognitive Disorganization/Psychosis”(PPP)
(Wisner et al; 1994)
• delirium; Impaired Sensorium delirium; Impaired Sensorium
• cognitive disorganizationcognitive disorganization
• visual, tactile and olfactory hallucinationsvisual, tactile and olfactory hallucinations
• bizarre behavior
• self-neglectWaxing and waning presentation
***Psychiatric emergency***
PPP is BPD?? (Chaudron 2003)
• Bipolar women– high risk for postpartum episode
– (Liebenluft ‘96)
– highest rates of PPP in general population– (Jones and Craddock 2001, Reich and Winokur, 1970)
– high rates of PP relapse– (Marks et al, 1992, Dean et al. 1989)
– FH of PPP– (Jones and Craddock 2001, Reich and Winokur, 1970,
Dean et al, 1989))
NEUROHORMONES & CNS
E2 PROG MAO / COMT
E2 MAO & COMT 5HT
PROG MAO & COMT SHT
MAO: Monoamine Oxidase
COMT: Catechol-O-Methyl Transferase
Estrogen TRYP
5HT Re-uptake Site5HT
Hypothalamic Pituitary Ovarian Axis (HPO)
Brain 5HT
EPI
DA
Brain
placenta
estrogencortisol, androgenhCG, hPL, LH, FSH
progesterone thyroid prolactin
PREGNANCY 3 PREGNANCY 4
PREGNANCY 5
SPIRAL INTO MENTAL ILLNESS(Denno, 2003)
PREGNANCY 1
MEDS: HALDOL, REMERON, EFFEXOR
PREGNANCY 2
•PPD, VH
PPD, D/C JOGGING, SWIMMING, SOCIAL WD
PPP: 2 HOSPITALIZATIONS: PSYCHOSIS AND SUICIDE, “DESPONDENT,” DISCHARGE BECAUSE OF INSURANCE
PPP: 2 HOSPITALIZATIONS, “CATATONIC” 24 HOUR WATCH
•JUNE 6, 2001: HALDOL D/Cd, EFFEXOR, REMERON 40 MG/D
•**NO MOOD STABILIZER**
ISOLATION AND PSYCHOSOCIAL
STRESSORS
STIGMA AND EDUCATION
SERIES OF ERRORS…….(Denno, 2003).
PH, FH PSYCH
PROFESSIONAL
H/O CHILDBIRTH
•BPD: FATHER, BROTHER MDD: MOTHER, SISTER , BROTHER
1994-2001: PREGNANT OR LACTATING
•HOMESCHOOLING; BIBLE STUDY ETC.
•COUPLE, FAMILY, NEIGHBORS
•PSYCHIATRY, CHILD SERVICES, LEGAL COMMUNITY
HOSPITAL
JUDICIAL SYSTEM
SOCIETY’S FAILUREMEDICAL
MANAGEMENT
PUBLIC EDUCATION
•MEDICATION, SAFETY
•MD, NURSES, HMO
ARCHAIC LAWS
DEATH PENALTY JURY
JURY ? TREATMENT
FAMILY: MENTAL HEALTH
NEIGHBOR: “CAGED ANIMAL”
‘The infant's life is a vulnerable thing and depends
to a great extent on the mother's good will. Sara
Ruddick (1989) has captured the contradictions
well in noting that mothers, while so totally in
control of the lives and well being of their infants
and small babies, are themselves under the
dominion and control of others…...